The purpose of the project is to investigate the biological roles of members of the chemokine family of cytokines by studying the actions of chemokines and their receptors in vivo, particularly in mouse models of infectious disease and inflammation. Chemokines and their receptors are critical for leukocyte trafficking. Our experiments will provide important information for understanding in which therapeutic contexts in humans manipulating the chemokine system might be beneficial. This laboratory discovered two mouse chemokines, Crg-2/CXCL10 and Mig/CXCL9 that are highly induced by gamma interferon. We discovered human - and cloned the mouse analogue of - CCR6, the receptor for the chemokine MIP-3alpha/CCL20 and reportedly for the beta-defensin anti-microbial peptides. We also cloned and characterized the human CCR9A and CCR9B, receptors for the chemokine TECK/CCL25. Part of this project uses gene-targeted mice that we have made (CXCL9 and CCR6 knockout mice) to investigate the roles of these ligand/receptor groups in models of immunity and inflammation in mice. In addition, we have produced polyclonal and monoclonal neutralizing antibodies to block the actions of mouse chemokines in vivo. Collaborative work in the last year has revealed that CXCL9 inhibits the recruitment of eosinophils into the lung in a mouse model of allergic airway inflammation. These results may suggest pathways of allergic inflammation that can be targeted for therapeutic benefit.